4.6 Review

Druggable genome and precision medicine in cancer: current challenges

Journal

FEBS JOURNAL
Volume 288, Issue 21, Pages 6142-6158

Publisher

WILEY
DOI: 10.1111/febs.15788

Keywords

biobanking; drug resistance; druggable genome; oncogenes; organoids; personalized therapeutics; precision medicine

Funding

  1. EKFS (SUNMAPK) [CRC 1292]
  2. Deutsche Krebs Hilfe [DKH 70113042]
  3. Forschungszentrum fur Immuntherapie of the University Medical Center Mainz
  4. DFG [RA1739/4-1]
  5. GFK fellowship

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Recent advances in cancer therapy have provided hope for patients through the development of specific treatment options, but drug resistance remains a challenge. The integration of multidisciplinary approaches has led to the development of next generation therapeutics, and the combination of immune checkpoint inhibitors in synergistic therapeutic regimes offers new promise for cancer patients.
The past decades have seen tremendous developments with respect to specific therapeutics that target key signaling molecules to conquer cancer. The key advancements with multiomics technologies, especially genomics, have allowed physicians and molecular oncologists to design tailor-made solutions to the specific oncogenes that are deregulated in individual patients, a strategy which has turned out to be successful though the patients quickly develop resistance. The swift integration of multidisciplinary approaches has led to the development of next generation therapeutics and, with synergistic therapeutic regimes combined with immune checkpoint inhibitors to reactivate the dampened immune response, has provided the much-needed promise for cancer patients. Despite these advances, a large portion of the druggable genome remains understudied, and the role of druggable genome in the immune system needs further attention. Establishment of patient-derived organoid models has fastened the preclinical validation of novel therapeutics for swift clinical translation. We summarized the current advances and challenges and also stress the importance of biobanking and collection of longitudinal data sets with structured clinical information, as well as the critical role these high content data sets will play in designing new therapeutic regimes in a tailor-made fashion.

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